A prospective study of lymphocyte-initiated immunosuppression in normal pregnancy: evidence of a T-cell etiology for postpartum thyroid dysfunction.
A prospective study of lymphocyte-initiated immunosuppression in normal pregnancy: evidence of a T-cell etiology for postpartum thyroid dysfunction.
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DOI：
10.1210/jcem.74.3.1740500
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发表时间：
1992-03
期刊：
影响因子：
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通讯作者：
A. Stagnaro-Ǵreen;S. Roman;R. Cobin;Essam El-Harazy;S. Wallenstein;T. Davies
中科院分区：
文献类型：
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作者：
A. Stagnaro-Ǵreen;S. Roman;R. Cobin;Essam El-Harazy;S. Wallenstein;T. Davies
正常妊娠和产后期的免疫功能仍然不清楚。我们假设，对免疫功能正常和异常的孕妇进行比较研究，将有助于我们进一步了解妊娠的免疫机制。我们选择研究一组有产后甲状腺功能障碍（PPTD）风险的孕妇以及一组正常对照。我们选择PPTD作为异常免疫功能的模型，因为在早期研究中，PPTD相对容易监测疾病的发展和相对较高的患病率。552名妇女在怀孕的前三个月进行了甲状腺自身抗体的筛查。33名甲状腺自身抗体阳性妇女和28名甲状腺自身抗体阴性妇女在整个妊娠期和产后6个月进行前瞻性随访。淋巴细胞亚群分析，甲状腺功能试验，甲状腺自身抗体（抗人甲状腺球蛋白和抗甲状腺过氧化物酶）进行了规定的时间间隔。所有患者均进行了HLA血清学分型。正常妊娠的主要特征是CD 4 + T细胞减少和CD 8 + T细胞增加，导致妊娠晚期和产后期CD 4 +/CD 8+比值显著下降。发生PPTD的妇女有1）更高的CD 4 +/CD 8+比值（P = 0.04），2）产后期T细胞活化（P = 0.02），3）甲状腺自身抗体滴度（抗人甲状腺球蛋白，P = 0.02;抗甲状腺过氧化物酶，P = 0.0018）显著更高。我们发现PPTD的总发病率为8.8%。这些数据表明，在妊娠前三个月甲状腺自身抗体阳性的妇女有三分之一的机会发展为PPTD。我们观察到正常孕妇的辅助/抑制T细胞比例显著下降，这与明显的T细胞亚群变化有关。这种妊娠启动的T细胞调节反映了免疫功能的整体抑制。PPTD的发展是我们人群中常见的产后事件，与三联免疫标志物相关：妊娠正常免疫抑制减少（如较高的T细胞辅助/抑制比值所示），产后T细胞活化增强，甲状腺自身抗体升高。因此，免疫抑制程度的降低是PPTD发展的主要因素。我们的研究结果定义了正常妊娠中发生的免疫学变化和PPTD发展所需的独特免疫学异常。
Immune function in normal pregnancy and the postpartum period remains poorly defined. We hypothesized that a comparative study between pregnant women with normal and abnormal immune function would further our understanding of the immune mechanisms of pregnancy. We chose to study a cohort of pregnant women at risk for the development of postpartum thyroid dysfunction (PPTD) as well as a group of normal controls. We chose PPTD as the model for abnormal immune function because of the relative ease of monitoring disease development and the relatively high prevalence for PPTD reported in earlier studies. Five hundred and fifty-two women were screened for the presence of thyroid autoantibodies in the first trimester of pregnancy. Thirty-three thyroid autoantibody-positive women and 28 thyroid autoantibody-negative women were followed prospectively throughout pregnancy and 6 months into the postpartum period. Lymphocyte subset analyses, thyroid function tests, and thyroid autoantibodies (antihuman thyroglobulin and antithyroid peroxidase) were performed at defined intervals. All patients were HLA serotyped. Normal pregnancy was principally characterized by decreased CD4+ T-cells and increasing CD8+ T-cells, causing a significant fall in the CD4+/CD8+ ratio in late pregnancy and into the postpartum period. Women who developed PPTD had 1) a higher CD4+/CD8+ ratio (P = 0.04), 2) activation of T-cells in the postpartum period (P = 0.02), and 3) significantly higher thyroid autoantibody titers (antihuman thyroglobulin, P = 0.02; antithyroid peroxidase, P = 0.0018). We found an overall incidence for PPTD of 8.8%. These data demonstrated that women who were thyroid autoantibody positive in the first trimester of pregnancy had a one in three chance of developing PPTD. We observed a significant fall in the T-cell helper/suppressor ratio in normal pregnant women, which was associated with distinct T-cell subset changes. This pregnancy-initiated T-cell regulation reflected an overall suppression of immune function. The development of PPTD was a frequent postpartum event in our population and was associated with a triad of immune markers: a reduction in the normal immune suppression of pregnancy (as indicated by higher T-cell helper/suppressor ratios), enhanced postpartum T-cell activation, and elevated thyroid autoantibodies. The reduction in the degree of immune suppression was, therefore, a major factor in the development of PPTD. Our results define immunological changes that occur in normal pregnancy and distinct immunological abnormalities necessary for the development of PPTD.